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Deep Learning Technology: Sebastian Arnold, Betty van Aken, Paul Grundmann, Felix A. Gers and Alexander Löser. Learning Contextualized Document Representations for Healthcare Answer Retrieval. The Web Conference 2020 (WWW'20)
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Drug use during pregnancy can have temporary or permanent effects on the fetus. Any drug that acts during embryonic or fetal development to produce a permanent alteration of form or function is known as a teratogen. Drugs may refer to both pharmaceutical drug and recreational drugs.
Each year, ill health as a result of pregnancy is experienced (sometimes permanently) by more than 20 million women around the world. In 2013 complications of pregnancy resulted in 293,000 deaths down from 377,000 deaths in 1990. Common causes include maternal bleeding (44,000), complications of abortion (44,000), high blood pressure of pregnancy (29,000), maternal sepsis (24,000), and obstructed labor (19,000).
The following are some examples of pregnancy complications:
- Pregnancy induced hypertension
- Anemia
- Postpartum depression
- Postpartum psychosis
- Thromboembolic disorders. These are the leading cause of death in pregnant women in the US.
- PUPPP (Pruritic Urticarial Papules and Plaques of Pregnancy), a skin disease that develops around the 32nd week. Signs are red plaques, papules, and itchiness around the belly button that then spreads all over the body except for the inside of hands and face.
- Ectopic pregnancy, implantation of the embryo outside the uterus.
- Hyperemesis gravidarum, excessive nausea and vomiting that is more severe than normal morning sickness.
- Pulmonary embolism, blood clots that form in the legs that can migrate to the lungs.
There is also an increased susceptibility and severity of certain infections in pregnancy.
The symptoms and discomforts of pregnancy are those presentations and conditions that result from pregnancy but do not significantly interfere with activities of daily living or pose a threat to the health of the mother or baby. This is in contrast to pregnancy complications. Sometimes a symptom that is considered a discomfort can be considered a complication when it is more severe. For example, nausea (morning sickness) can be a discomfort, but if, in combination with significant vomiting it causes a water-electrolyte imbalance, it is a complication known as hyperemesis gravidarum.
Common symptoms and discomforts of pregnancy include:
- Tiredness.
- Constipation
- Pelvic girdle pain
- Back pain
- Braxton Hicks contractions. Occasional, irregular, and often painless contractions that occur several times per day.
- Edema (swelling). Common complaint in advancing pregnancy. Caused by compression of the inferior vena cava and pelvic veins by the uterus leads to increased hydrostatic pressure in lower extremities.
- Increased urinary frequency. A common complaint, caused by increased intravascular volume, elevated glomerular filtration rate, and compression of the bladder by the expanding uterus.
- Urinary tract infection
- Varicose veins. Common complaint caused by relaxation of the venous smooth muscle and increased intravascular pressure.
- Haemorrhoids (piles). Swollen veins at or inside the anal area. Caused by impaired venous return, straining associated with constipation, or increased intra-abdominal pressure in later pregnancy.
- Regurgitation, heartburn, and nausea.
- Stretch marks
- Breast tenderness is common during the first trimester, and is more common in women who are pregnant at a young age.
In addition, pregnancy may result in pregnancy complication such as deep vein thrombosis or worsening of an intercurrent disease in pregnancy.
Swelling (especially in the hands and face) was originally considered an important sign for a diagnosis of pre-eclampsia. However, because swelling is a common occurrence in pregnancy, its utility as a distinguishing factor in pre-eclampsia is not high. Pitting edema (unusual swelling, particularly of the hands, feet, or face, notable by leaving an indentation when pressed on) can be significant, and should be reported to a health care provider.
In general, none of the signs of pre-eclampsia are specific, and even convulsions in pregnancy are more likely to have causes other than eclampsia in modern practice. Further, a symptom such as epigastric pain may be misinterpreted as heartburn. Diagnosis, therefore, depends on finding a coincidence of several pre-eclamptic features, the final proof being their regression after delivery.
HELLP syndrome is defined as hemolysis (microangiopathic), elevated liver enzymes (liver dysfunction), and low platelets (thrombocytopenia). This condition may occur in 10–20% of patients with severe pre-eclampsia and eclampsia and is associated with increased maternal and fetal morbidity and mortality. In 50% of instances, HELLP syndrome develops preterm, while 20% of cases develop in late gestation and 30% during the post-partum period.
Women with placenta previa often present with painless, bright red vaginal bleeding. This commonly occurs around 32 weeks of gestation, but can be as early as late mid-trimester. 51.6% of women with placenta previa have antepartum haemorrhage. This bleeding often starts mildly and may increase as the area of placental separation increases. Previa should be suspected if there is bleeding after 24 weeks of gestation. Bleeding after delivery occurs in about 22% of those affected.
Women may also present as a case of failure of engagement of fetal head.
Rh disease (also known as rhesus isoimmunisation, Rh (D) disease, rhesus incompatibility, rhesus disease, RhD hemolytic disease of the newborn, rhesus D hemolytic disease of the newborn or RhD HDN) is a type of hemolytic disease of the newborn (HDN). The disease ranges from mild to severe, and typically occurs only in some second or subsequent pregnancies of Rh negative women where the fetus's father is Rh positive, leading to a Rh+ pregnancy. During birth, the mother may be exposed to the infant's blood, and this causes the development of antibodies, which may affect the health of subsequent Rh+ pregnancies. In mild cases, the fetus may have mild anaemia with reticulocytosis. In moderate or severe cases the fetus may have a more marked anaemia and erythroblastosis fetalis (hemolytic disease of the newborn). When the disease is very severe it may cause hydrops fetalis or stillbirth.
Rh disease is generally preventable by treating the mother during pregnancy or soon after delivery with an intramuscular injection of anti-RhD immunoglobulin (Rho(D) immune globulin). The RhD protein is coded by the RHD gene.
Large for gestational age (LGA) is an indication of high prenatal growth rate.
LGA is often defined as a weight, length, or head circumference that lies above the 90th percentile for that gestational age. However, it has been suggested that the definition be restricted to infants with birth weights greater than the 97th percentile (2 standard deviations above the mean) as this more accurately describes infants who are at greatest risk for perinatal morbidity and mortality.
Macrosomia, which literally means "long body", is sometimes confused with LGA. Some experts consider a baby to be big when it weighs more than at birth, and others say a baby is big if it weighs more than . A baby is also called “large for gestational age” if its weight is greater than the 90th percentile at birth.
Developmental toxicity is any structural or functional alteration, reversible or irreversible, which interferes with homeostasis, normal growth, differentiation, development or behavior, and which is caused by environmental insult (including drugs, lifestyle factors such as alcohol, diet, and environmental toxic chemicals or physical factors). It is the study of adverse effects on the development of the organism resulting from exposure to toxic agents before conception (either parent), during prenatal development, or post-natally until puberty. The substance that causes developmental toxicity from embryonic stage to birth is called teratogens. The effect of the developmental toxicants depends on the type of substance, dose and duration and time of exposure.
Certain Pathogens are also included since the toxins they secrete are known to cause adverse effects on the development of the organism when the mother or fetus is infected. Developmental toxicology is a science studying adverse developmental outcomes. This term has widely replaced the early term for the study of primarily structural congenital abnormalities, teratology, to enable inclusion of a more diverse spectrum of congenital disorders. Typical factors causing developmental toxicity are radiation, infections (e.g. rubella), maternal metabolic imbalances (e.g. alcoholism, diabetes, folic acid deficiency), drugs (e.g. anticancer drugs, tetracyclines, many hormones, thalidomide), and environmental chemicals (e.g. mercury, lead, dioxins, PBDEs, HBCD, tobacco smoke). The first-trimester exposure is considered the most potential for developmental toxicity.
Once fertilization has taken place, the toxicants in the environment can pass through the mother to the developing embryo or fetus across the placental barrier. The fetus is at greatest risk during the first 14th to 60th day of the pregnancy when the major organs are being formed. However, depending on the type of toxicant and amount of exposure, a fetus can be exposed toxicant at any time during pregnancy. For example, exposure to a particular toxicant at one time in the pregnancy may result in organ damage and at another time in the pregnancy could cause death of the fetus and miscarriage. There are a number of chemicals, biological agents (such as bacteria and viruses), and physical agents (such as radiation) used in a variety of workplaces that are known to cause developmental disorders. Developmental disorders can include a wide range of physical abnormalities, such as bone or organ deformities, or behavioral and learning problems, such as a mental retardation. Exposures to some chemicals during pregnancy can lead to the development of cancer later in the life of the child and are called transgenerational carcinogens. Exposure to toxicants during the second and the third trimester of a pregnancy can lead to slow fetal grown and result in low birth weight.
The apprehension is not necessarily data driven and is a cautionary response to the lack of clinical studies in pregnant women. The indication is a trade-off between the adverse effects of the drug, the risks associated with intercurrent diseases and pregnancy complications, and the efficiency of the drug to prevent or ameliorate such risks. In some cases, the use of drugs in pregnancy carries benefits that outweigh the risks. For example, high fever is harmful for the fetus in the early months, thus the use of paracetamol (acetaminophen) is generally associated with lower risk than the fever itself. Similarly, diabetes mellitus during pregnancy may need intensive therapy with insulin to prevent complications to mother and baby. Pain management for the mother is another important area where an evaluation of the benefits and risks is needed. NSAIDs such as Ibuprofen and Naproxen are probably safe for use for a short period of time, 48–72 hours, once the mother has reached the second trimester. If taking aspirin for pain management the mother should never take a dose higher than 100 mg.
The pregnancy category of a medication is an assessment of the risk of fetal injury due to the pharmaceutical, if it is used as directed by the mother during pregnancy. It does "not" include any risks conferred by pharmaceutical agents or their metabolites in breast milk.
Every drug has specific information listed in its product literature. The British National Formulary used to provide a table of drugs to be avoided or used with caution in pregnancy, and did so using a limited number of key phrases, but now Appendix 4 (which was the Pregnancy table) has been removed. Appendix 4 is now titled "Intravenous Additives". However, information that was previously available in the former Appendix 4 (pregnancy) and Appendix 5 (breast feeding) is now available in the individual drug monographs.
LGA and macrosomia cannot be diagnosed until after birth, as it is impossible to accurately estimate the size and weight of a child in the womb. Babies that are large for gestational age throughout the pregnancy may be suspected because of an ultrasound, but fetal weight estimations in pregnancy are quite imprecise. For non-diabetic women, ultrasounds and care providers are equally inaccurate at predicting whether or not a baby will be big. If an ultrasound or a care provider predicts a big baby, they will be wrong half the time.
Although big babies are born to only 1 out of 10 women, the 2013 Listening to Mothers Survey found that 1 out of 3 American women were told that their babies were too big. In the end, the average birth weight of these suspected “big babies” was only . In the end, care provider concerns about a suspected big baby were the fourth-most common reason for an induction (16% of all inductions), and the fifth-most common reason for a C-section (9% of all C-sections). This treatment is not based on current best evidence.
Research has consistently shown that, as far as birth complications are concerned, the care provider’s perception that a baby is big is more harmful than an actual big baby by itself. In a 2008 study, researchers compared what happened to women who were suspected of having a big baby to what happened to women who were not suspected of having a big baby—but who ended up having one. In the end, women who were suspected of having a big baby (and actually had one) had a triple in the induction rate, more than triple the C-section rate, and a quadrupling of the maternal complication rate, compared to women who were not suspected of having a big baby but who had one anyway.
Complications were most often due to C-sections and included bleeding (hemorrhage), wound infection, wound separation, fever, and need for antibiotics. There were no differences in shoulder dystocia between the two groups. In other words, when a care provider “suspected” a big baby (as compared to not knowing the baby was going to be big), this tripled the C-section rates and made mothers more likely to experience complications, without improving the health of babies.
Placenta praevia is when the placenta attaches inside the uterus but near or over the cervical opening. Symptoms include vaginal bleeding in the second half of pregnancy. The bleeding is bright red and tends not to be associated with pain. Complications may include placenta accreta, dangerously low blood pressure, or bleeding after delivery. Complications for the baby may include fetal growth restriction.
Risk factors include pregnancy at an older age and smoking as well as prior cesarean section, labor induction, or termination of pregnancy. Diagnosis is by ultrasound. It is classified as a complication of pregnancy.
For those who are less than 36 weeks pregnant with only a small amount of bleeding recommendations may include bed rest and avoiding sexual intercourse. For those after 36 weeks of pregnancy or with a significant amount of bleeding, cesarean section is generally recommended. In those less than 36 weeks pregnant, corticosteroids may be given to speed development of the babies lungs. Cases that occur in early pregnancy may resolve on their own.
It affects approximately 0.5% of pregnancies. After four cesarean section it, however, effects 10% of pregnancies. Rates of disease have increased over the late 20th century and early 21st century. The condition was first described in 1685 by Paul Portal.
Hemolytic disease of the newborn (anti-Rhc) can range from a mild to a severe disease. It is the third most common cause of severe HDN. Rh disease is the most common and hemolytic disease of the newborn (anti-Kell) is the second most common cause of severe HDN.
It occurs more commonly in women who are Rh D negative.
Acute fatty liver of pregnancy (or hepatic lipidosis of pregnancy) usually manifests in the third trimester of pregnancy, but may occur any time in the second half of pregnancy, or in the puerperium, the period immediately after delivery. On average, the disease presents during the 35th or 36th week of pregnancy. The usual symptoms in the mother are non-specific including nausea, vomiting, anorexia (or lack of desire to eat) and abdominal pain; excessive thirst may be the earliest symptom without overlap with otherwise considered normal pregnancy symptoms; however, jaundice and fever may occur in as many as 70% of patients.
In patients with more severe disease, pre-eclampsia may occur, which involves elevation of blood pressure and accumulation of fluid (termed oedema). This may progress to involvement of additional systems, including acute renal failure, hepatic encephalopathy, and pancreatitis. There have also been reports of diabetes insipidus complicating this condition.
Many laboratory abnormalities are seen in acute fatty liver of pregnancy. Liver enzymes are elevated, with the AST and ALT enzymes ranging from minimal elevation to 1000 IU/L, but usually staying in the 300-500 range. Bilirubin is almost universally elevated. Alkaline phosphatase is often elevated in pregnancy due to production from the placenta, but may be additionally elevated. Other abnormalities may include an elevated white blood cell count, hypoglycemia, elevated coagulation parameters, including the international normalized ratio, and decreased fibrinogen. Frank disseminated intravascular coagulation, or DIC, may occur in as many as 70% of people.
Abdominal ultrasound may show fat deposition in the liver, but, as the hallmark of this condition is microvesicular steatosis (see pathology below), this is not seen on ultrasound. Rarely, the condition can be complicated by rupture or necrosis of the liver, which may be identified by ultrasound.
Up to 10% of women with ectopic pregnancy have no symptoms, and one-third have no medical signs. In many cases the symptoms have low specificity, and can be similar to those of other genitourinary and gastrointestinal disorders, such as appendicitis, salpingitis, rupture of a corpus luteum cyst, miscarriage, ovarian torsion or urinary tract infection. Clinical presentation of ectopic pregnancy occurs at a mean of 7.2 weeks after the last normal menstrual period, with a range of 4 to 8 weeks. Later presentations are more common in communities deprived of modern diagnostic ability.
Signs and symptoms of ectopic pregnancy include increased hCG, vaginal bleeding (in varying amounts), sudden lower abdominal pain, pelvic pain, a tender cervix, an adnexal mass, or adnexal tenderness. In the absence of ultrasound or hCG assessment, heavy vaginal bleeding may lead to a misdiagnosis of miscarriage. Nausea, vomiting and diarrhea are more rare symptoms of ectopic pregnancy.
Rupture of an ectopic pregnancy can lead to symptoms such as abdominal distension, tenderness, peritonism and hypovolemic shock. A woman with ectopic pregnancy may be excessively mobile with upright posturing, in order to decrease intrapelvic blood flow, which can lead to swelling of the abdominal cavity and cause additional pain.
Fetal alcohol spectrum disorders (FASD) is a term that constitutes the set of conditions that can occur in a person whose mother drank alcohol during the course of pregnancy. These effects can include physical and cognitive problems. FASD patient usually has a combination of these problems. Extent of effect depends on exposure frequency, dose and rate of ethanol elimination from amniotic fluid. FAS disrupts normal development of the fetus, which may cause certain developmental stages to be delayed, skipped, or immaturely developed. Since alcohol elimination is slow in a fetus than in an adult and the fact that they do not have a developed liver to metabolize the alcohol, alcohol levels tend to remain high and stay in the fetus longer. Birth defects associated with prenatal exposure to alcohol can occur in the first three to eight weeks of pregnancy before a woman even knows that she is pregnant.
The most common complication is rupture with internal bleeding which may lead to hypovolemic shock. Death from rupture is still the leading cause of death in the first trimester of the pregnancy.
Cannabis consumption in pregnancy might be associated with restrictions in growth of the fetus, miscarriage, and cognitive deficits. The American Congress of Obstetricians and Gynecologists recommended that cannabis use be stopped before and during pregnancy, Cannabis is the most commonly used illicit substance
among pregnant women.
Although it is difficult to draw firm conclusions, there is some evidence that prenatal exposure to marijuana may be associated with deficits in language, attention, cognitive performance, and delinquent behaviors. THC exposure in rats during the prenatal developmental phase may cause epigenetic changes in gene expression, but there is limited knowledge about the risk for psychiatric disorders because of ethical barriers to studying the developing human brain. While animal studies cannot take into account factors that could influence the effects of cannabis on human maternal exposure, such as environmental and social factors, a 2011 review of rodent studies by Campolongo "et al." said there was "... increasing evidence from animal studies showing that cannabinoid drugs ... induce enduring neurobehavioral abnormalities in the exposed offspring ..." Campolongo "et al." added that "clinical studies report hyperactivity, cognitive impairments and altered emotionality in humans exposed in utero to cannabis". Martin "et al." investigated recent trends in substance abuse treatment admissions for cannabis use in pregnancy in the US, based on Treatment Episodes Data Set (TEDS) from 1992 to 2012, and discovered that, while the proportion of treatment admissions for pregnant women was stable (about 4%), the admissions for women who were pregnant and reported any marijuana use grew from 29% to 43%. A 2015 review found that cannabis use by pregnant mothers impaired brain maturation in their children, and that it also predisposed their children to neurodevelopmental disorders.
Hemolytic disease of the newborn, also known as hemolytic disease of the fetus and newborn, HDN, HDFN, or erythroblastosis fetalis, is an alloimmune condition that develops in a fetus, when the IgG molecules (one of the five main types of antibodies) produced by the mother pass through the placenta. Among these antibodies are some which attack antigens on the red blood cells in the fetal circulation, breaking down and destroying the cells (hemolysis). The fetus can develop reticulocytosis and anemia. This fetal disease ranges from mild to very severe, and fetal death from heart failure (hydrops fetalis) can occur. When the disease is moderate or severe, many erythroblasts (immature red blood cells) are present in the fetal blood, and so these forms of the disease can be called "erythroblastosis fetalis" (or "erythroblastosis foetalis").
HDFN represents a breach of immune privilege for the fetus or some other form of impairment of the immune tolerance of pregnancy. Various types of HDFN are classified by which alloantigen provokes the response. In order of incidence, the types include ABO, anti-RhD, anti-RhE, anti-Rhc, anti-Rhe, anti-RhC, multiantigen combinations, and anti-Kell.
The signs and symptoms of a vertically transmitted infection depend on the individual pathogen. It may cause subtle signs such as a influenza-like illness and may not even be noticed by the mother during the pregnancy. In such cases, the effects may be seen first at birth.
Symptoms of a vertically transmitted infection may include fever and flu like symptoms. The newborn is often small for gestational age. A petechial rash on the skin may be present, with small reddish or purplish spots due to bleeding from capillaries under the skin. An enlarged liver and spleen (hepatosplenomegaly) is common, as is jaundice. However, jaundice is less common in hepatitis B because a newborn's immune system is not developed well enough to mount a response against liver cells, as would normally be the cause of jaundice in an older child or adult. Hearing impairment, eye problems, mental retardation, autism, and death can be caused by vertically transmitted infections. The mother often has a mild infection with few or no symptoms.
The genetic conditions of Aicardi-Goutieres syndrome are possibly present in a similar manner.
Hemolytic disease of the newborn (anti-RhE) is caused by the anti-RhE antibody of the Rh blood group system. The anti-RhE antibody can be naturally occurring, or arise following immune sensitization after a blood transfusion or pregnancy.
The anti-RhE antibody is quite common especially in the Rh genotype CDe/CDe; It usually only causes a mild hemolytic disease, but can cause a severe condition in the newborn. It can occur with other antibodies, usually the anti-Rhc antibody, which can also cause a severe hemolytic disease.
One study done by Moran et al., found that titers are not reliable for anti-E. Their most severe case of hemolytic disease of the newborn occurred with titers 1:2. Moran states that it would be unwise routinely to dismiss anti-E as being of little clinical consequence.
HIV in pregnancy is the presence of the HIV virus in a woman while pregnant. There are concerns because women diagnosed with HIV/AIDS may transmit the infection to their child during pregnancy. The infection be transmitted to the infant during the pregnancy, childbirth, or breastfeeding. However, the risk of mother-to-child transmission of HIV may be reduced by the use of HIV medications known as antiretroviral therapy (ART). These medications may be used by women before, during, and after pregnancy. After delivery, children are also given the medication to reduce the risk of infection. Because HIV may be spread through breast milk, mothers with the infection are encouraged to avoid breastfeeding.
Infection with HIV/AIDS is not a contraindication to pregnancy. Women with the disease may choose to become pregnant if they desire, however, they are encouraged to talk with their doctors beforehand. Some women are unaware they have the disease until they become pregnant. In this case, they should begin antiretroviral therapy as soon as possible. With the appropriate treatment, the risk of mother-to-child infection can be reduced to below 1%. Without treatment, the risk of transmission is 15-45%.
There are approximately 1.4 million HIV positive women who become pregnant and contribute to more than 300,000 neonatal and fetal deaths each year. With the use of ART, transmission of HIV from the mother to child has decreased according to reports by the World Health Organization (WHO). In 2009, there were an estimated 400,000 children born with HIV and by 2013, there were 240,000. Countries in Southern Africa are worst affected by the HIV/AIDS pandemic. In 2010, 30% of all pregnancies in the region were affected by HIV. In 2011, HIV was responsible for 50% of the deaths for children below the age of 5. In the United States, fewer than 200 babies are born with HIV every year.
As of 2015, Cuba has become the first country in the world to eradicate mother-to-child transmission of HIV. In 2010, the WHO partnered with the Pan American Health Organization (PAHO) to implement an initiative that would provide early prenatal care and HIV testing for all pregnant women in the country. For women who tested positive, ART was provided for both the mother and child, cesarean sections were performed, and alternatives to breastfeeding were provided. In implementing these measures, the country was successfully able to eradicate HIV transmission during pregnancy.
A Rhc negative mother can become sensitised by red blood cell (RBC) Rhc antigens by her first pregnancy with a Rhc positive fetus. The mother can make IgG anti-Rhc antibodies, which are able to pass through the placenta and enter the fetal circulation. If the fetus is Rhc positive alloimmune hemolysis can occur leading to HDN. This is similar as for Rh disease, which is usually caused when a RhD negative mother is sensitised by her first pregnancy with a RhD positive fetus.
Sensitization to Rhc antigens can also be caused by blood transfusion.
Other conditions may commonly co-occur with FAS, stemming from prenatal alcohol exposure. However, these conditions are considered alcohol-related birth defects and not diagnostic criteria for FAS.
- Heart: A heart murmur that frequently disappears by one year of age. Ventricular septal defect most commonly seen, followed by an atrial septal defect.
- Bones: Joint anomalies including abnormal position and function, altered palmar crease patterns, small distal phalanges, and small fifth fingernails.
- Kidneys: Horseshoe, aplastic, dysplastic, or hypoplastic kidneys.
- Eyes: Strabismus, optic nerve hypoplasia (which may cause light sensitivity, decreased visual acuity, or involuntary eye movements).
- Occasional problems: ptosis of the eyelid, microophthalmia, cleft lip with or without a cleft palate, webbed neck, short neck, tetralogy of Fallot, coarctation of the aorta, spina bifida, and hydrocephalus.